This proposal is for a 5-year competing renewal of the UW Superfund Basic Research Program Project. The theme of this Program Project is that biomarkers measured in accessible tissues are predictive of: a) toxicant exposures; b) early indicators of damage; and/or c) unusual susceptibility to toxic agents that commonly occur at hazardous waste sites. The UW Program Project includes 9 research projects (7 biomedical, 2 bioremediation), an administrative core, a service core dedicated to molecular biology assays, a training core and an outreach core. The research projects can be divided into four subgroups: 1) laboratory-based development of sensitive biomarkers of adverse effects and disease susceptibility ; 2) applications of biomarkers to human populations. 4) biomarker measurements of environmental chemical toxicity in terrestrial and aquatic species and 4) biomarker applications for hazardous waste remediation. Multi-disciplinary cross-project interactions among toxicologists, epidemiologists, molecular biologists and environmental engineers (e.g. measurement of the same biomarkers in various projects to assess a range of effects) have been carefully devised to maximize scientific yield. This project will continue investigations in glutathione biosynthesis biomarker as indicators of oxidative to assess a range of effects) have been carefully devised to maximized scientific yield. This project will continue investigations on glutathione biosynthesis biomarker as indicators of oxidative stress; characterization of novel biomarkers and applications to epidemiologic investigations are newer directions. This project will continue investigations on glutathione biosynthesis biomarker as indicators of oxidative stress; characterization and novel biomarkers and applications to epidemiologic investigations are newer directions. This project will identify genetic polymorphisms of porphyrin synthesis enzymes, and test these as markers of neurobehavioral toxicity in mercury-exposed humans. This project is a new project that will investigate paraoxonase phenotype and genotype inter-relations, with applications to experimental toxicokinetic studies in rats and to an epidemiologic studies of parkinsonism. This project continues to examine epidemiologically the interactions between environmental toxicants and genetic polymorphisms of enzymes involved in xenobiotic activation and detoxification. This project will apply a physiologically-based toxicokinetic model derived from controlled human exposures to organic solvents to characterize determinants of uptake, metabolism, and excretion. This project continues to examine biomarkers of exposure and effect in wildlife residing near or in hazardous waste sites. This project is a continuing study of DNA oxidative damage in fish from polluted and reference water sites. This project will continue to evaluate the effectiveness of genetically- engineered trees for bioremediation of toxic chemicals (e.g., trichloroethylene). This project will involve laboratory and field genetically-engineered trees for bioremediation of toxic chemicals (e.g., trichloroethylene). This project will involve laboratory and field experiments of in situ engineering methods for bioremediation of chlorinated aliphatic toxicants. The Administrative Core, directed by the Program Director, will oversee all major budgetary and personnel aspects of the program project, will coordinate multi-disciplinary interactions among research projects and cores, and will assume responsibility for information dissemination and technology transfer. The Program Director will be advised by the Deputy Director, an Internal Executive Committee comprised of research and core directors, and an External Science Advisory Board that includes distinguished environmental scientists from academia and governmental agencies. The Bioanalytical Core will offer genotyping and/or DNA sequencing services to the research projects. The Training Core will ensure that doctoral students and post-doctoral fellows in Environmental Health and Civil Engineering receive cross-disciplinary classroom and research experience. The Outreach Core, which is a new intuitive for this Program Project, will be dedicated to the development of instructional materials relevant to hazardous waste contaminant issues, with an emphasis on biomarker applications for toxicity assessment and bioremediation. The principal audiences for outreach will be K-12 school teachers, health and engineering professionals, and interested community residents.